What I taught today: Axis specification

We began today with chocolate. Always a good thing at 8am, I think — so I brought a candy bar to class. Then I told the students that I loved and respected them all equally and that they all had equal potential, but that I was going to mark just one person as special by giving them that candy bar^*. So I asked them how I could decide who should get it, telling them right off that dividing it wasn't an allowed solution, and that yes, this could be an openly unfair process.

There were lots of suggestions: we could do it by random chance. I could throw it into the middle of the room and let them fight over it. We could analyze everyone's DNA and give it to the most average person...or the most genetically unusual. I could just give it to the first person to raise their hand, or the person closest to me, or the person farthest from me. We could have a competition of some sort, and the winner gets it. I could give it to the person who wants it most, or who needs it most.

The point I was making is that this is a common developmental problem, that you have a potentially uniform set of cells and that somehow one or a few have to be distinguished as different, and carry out a different genetic program than another set of cells. One cop-out is to invoke mosaicism: that is, they aren't uniform, but inherit different sets of cytoplasmic determinants that make them different from the very beginning, but that even in that case, these determinants aren't detailed enough to specify every single cell fate in most organisms. Even with an initial prepattern, you're eventually going to end up with a field of cells, like the dorsal side of the fly wing, and within that uniform field, some cells will have to be programmed to be epithelial, others to be bristles, others to be neurons. And that means that in every organism, even the most classically mosaic, you'll reach a point where cells have to process information from their environment and regulate to build differential structures.

And with that I went on to talk about some animals that were judged as being mostly mosaic in character: molluscs, tunicates, echinoderms, and nematodes. Even here, these animals all required complex molecular interactions to build their embryos.

For example, I'd earlier used echinoderms as classic examples of regulative development. You can dissociate them at the 4-cell stage and each blastomere can go on to build a complete embryo. But at the 8-cell stage, when the cleavage plane separates an animal half from a vegetal half, that's no longer true: the top four cells when isolated are animalized, forming only a ciliated ball, while the bottom four cells are vegetalized, only making a static blob with a bit of a skeleton inside. Clever experiments can quantitatively juggle these cells around, removing just the bottom 4 cells (the micromeres) at the 16-cell stage, or assembling composite embryos with different ratios of the different tiers of cells, and get different degrees of development. Even when you're discussing an organism in which you'd call the pattern of development mosaic, it absolutely depends on ongoing cell:cell signaling at every step, and the final form is a consequence of interactions within the embryo. It's a mosaic-regulative continuum.

I also described very superficially the work of Davidson and Cameron on specification events in echinoderms. These interactions can be drawn as a kind of genetic circuit diagram, where what you're seeing is the pattern of genes being switched on and off. We can describe a cell type as the output of mappable gene circuitry, and we can even identify modules of networks of genes associated with a particular kind of cell, and that we can also see a limited number of genes that mediate interactions.

Next week I promised to start going into more detail, when we start talking about early fly development and axis decisions. The next class we're actually going to switch gears a bit and discuss Sean Carroll's Endless Forms Most Beautiful.

Slides used in this talk (pdf).

^*Yeah, I lied again. I brought enough candy bars for everyone, and after we'd generated a list of ways to share just one, I gave them to everyone. They'll never trust me again.